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Peiming Zheng,1,* Haoliang Zhang,2,* Huijie Gao,3,* Jingfang Sun,2 Junmeng Li,4 Xiulei Zhang,5 Lan Gao,1 Ping Ma,2,6 Shibao Li2,6 1Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Henan University, Kaifeng 450001, People’s Republic of China; 4Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China; 5Department of Microbiome Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, People’s Republic of China; 6Medical Technology School of Xuzhou Medical University, Xuzhou 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lan Gao; Ping Ma Email gaolan8@126.com; pingm62@aliyun.comPurpose: Exosomes participate in cellular communications by transmitting active molecules, including long noncoding RNAs (lncRNAs) and are regarded as suitable candidates for disease diagnosis. This study aimed to identify gastric cancer (GC)-specific exosomal lncRNA and investigate the potential diagnostic value of plasma exosomal lncRNA in GC.Patients and Methods: Exosomes from the culture media (CM) of four GC cells (GCCs) and human gastric epithelial cells were isolated. Exosomal RNA was extracted, and lncRNA microarray assay was performed to identify GC-specific exosomal lncRNAs. The expression levels of the candidate exosomal lncRNAs were validated in 120 subjects via quantitative reverse transcription PCR (qRT-PCR). The receiver operating characteristic (ROC) curve and area under curve were used to estimate thediagnostic capacity. We investigated the potential relationship between plasma exosomal lncRNA expression and the clinicopathological parameters of GC.Results: A total of 199 exosomal lncRNAs were expressed at considerable higher levels in GCCs than those in normal controls, among which the top 10 upregulated lncRNAs were selected for further validation in cell, CM, and plasma. qRT-PCR revealed that lnc-SLC2A12-10:1 was remarkably upregulated in exosomes derived from patients with GC and GCCs. The area under the ROC curve was 0.776, which was higher than the diagnostic accuracies of CEA, CA 19– 9, and CA72– 4. The expression level of exosomal lnc-SLC2A12-10:1 was also significantly correlated with tumor size, TNM stage, lymph node metastasis, and degree of differentiation. The postoperative expression levels of exosomal lnc-SLC2A12-10:1 were lower compared with those of preoperative levels.Conclusion: Our study suggested that exosomal lnc-SLC2A12-10:1 may be a potential noninvasive biomarker for the diagnosis and prognosis monitoring of GC. Further large-scale studies are necessary to validate its performance in GC progression.Keywords: exosomes, biomarker, gastric cancer, long noncoding RNA, diagnosis

Purpose Exosome-shuttled bioactive long non-coding RNA, as novel non-invasive biomarkers for cancer diagnosis, has received increasing attention. Here, we aimed to investigate the expression of serum exosomal long non-coding RNA pcsk2-2:1 (Exo-Lnc RNApcsk2-2:1) in patients of gastric cancer and evaluate its diagnostic value as a marker. Patients and methods Exosomes were isolated from serum sample of gastric cancer using HiPure Exosomekits and identified via transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. The total exosomal RNA was extracted and reverse transcribed to cDNA. The expression of Exo-Lnc RNA PCSK2-2:1 was detected in serum exosomes of 29 healthy people and 63 gastric cancer patients by real-time quantitative reverse transcription PCR (qRT-PCR), and the relationship between the expression level of Exo-Lnc RNA PCSK2-2:1 and clinicopathological parameters of patients was analyzed. Finally, a receiver operating characteristic curve was used to evaluate the clinical value of Exo-Lnc RNA PCSK2-2:1 as an auxiliary diagnostic marker for gastric cancer. Results Transmission electron microscopy, nanoparticle size analysis, and Western blotting showed successful separation of serum exosomes. qRT-PCR results revealed that compared with the healthy control, Lnc RNA PCSK2-2:1 expression level in serum exosomes of gastric cancer patients was significantly downregulated (p=0.006). Moreover, the expression level of Exo-Lnc RNA PCSK2-2:1 was correlated with tumor size (p=0.0441), tumor stage (p=0.0061), and venous invasion (p=0.0367). The area under the curve of Exo-Lnc RNA PCSK2-2:1 was 0.896. At the optimal cut-off value, the diagnostic sensitivity and specificity were 84% and 86.5%, respectively. Conclusion Our data indicate that Exo-Lnc RNA PCSK2-2:1 may perform a vital role in the progression of gastric cancer and can be used as a potential marker for the diagnosis of gastric cancer., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/3tU5Ca0Aqis